“Histamine H4 receptor”的意思、由来-开放百科全书

The histamine H₄ receptor is, like the other three histamine receptors, a member of the G protein-coupled receptor superfamily.^[1]^[2]^[3]

Discovery

Unlike the histamine receptors discovered earlier, H₄ was found in 2000 through a search of the human genomic DNA data base.^[4]

Tissue distribution

H₄ is highly expressed in bone marrow and white blood cells and regulates neutrophil release from bone marrow and subsequent infiltration in the zymosan-induced pleurisy mouse model.^[5] It is also expressed in the colon, liver, lung, small intestine, spleen, testes, thymus, tonsils, and trachea.^[6] It was also found that H4R exhibits a uniform expression pattern in the human oral epithelium. ^[7]

Function

The Histamine H4 receptor has been shown to be involved in mediating eosinophil shape change and mast cell chemotaxis.^[8] This occurs via the βγ subunit acting at phospholipase C to cause actin polymerisation and eventually chemotaxis.

Structure

The 3D structure of the H4 receptor has not been solved yet due to the difficulties of GPCR crystallization. Some attempts have been made to develop structural models of the H₄ receptor for different purposes. The first H₄ receptor model^[9] was built by homology modelling based on the crystal structure of bovine rhodopsin.^[10] This model was used for the interpretation of site-directed mutagenesis data, which revealed the crucial importance of Asp94 (3.32) and Glu182 (5.46) residues in ligand binding and receptor activation.

A second rhodopsin based structural model of the H₄ receptor was successfully used for the identification of novel H₄ ligands.^[11]

Recent advancements in GPCR crystallization, in particular the determination of the human histamine H₁ receptor in complex with doxepin^[12] will likely increase the quality of novel structural H₄ receptor models.^[13]^[14]

Ligands

Agonists

Antagonists

Therapeutic potential

The highly selective histamine H₄ antagonist VUF-6002 is orally active and inhibits the activity of both mast cells and eosinophils in vivo,^[16] and has antiinflammatory and antihyperalgesic effects.^[17]

References

1. ^{{cite journal |vauthors=Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S | title = Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes | journal = J. Biol. Chem. | volume = 275 | issue = 47 | pages = 36781–6 | year = 2000 | pmid = 10973974 | doi = 10.1074/jbc.M006480200 }}
2. ^{{cite journal |vauthors=Nakamura T, Itadani H, Hidaka Y, Ohta M, Tanaka K | title = Molecular cloning and characterization of a new human histamine receptor, HH4R | journal = Biochem. Biophys. Res. Commun. | volume = 279 | issue = 2 | pages = 615–20 | year = 2000 | pmid = 11118334 | doi = 10.1006/bbrc.2000.4008 }}
3. ^{{cite journal |vauthors=Nguyen T, Shapiro DA, George SR, Setola V, Lee DK, Cheng R, Rauser L, Lee SP, Lynch KR, Roth BL, O'Dowd BF | title = Discovery of a novel member of the histamine receptor family | journal = Mol. Pharmacol. | volume = 59 | issue = 3 | pages = 427–33 | year = 2001 | pmid = 11179435 | doi = 10.1124/mol.59.3.427| issn = | url = http://molpharm.aspetjournals.org/cgi/content/abstract/59/3/427 | format = abstract }}
4. ^{{cite journal |vauthors=Oda T, Morikawa N, Saito Y, Masuho Y, Matsumoto S|title=Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes |journal=J. Biol. Chem. |volume=275 |number=47 |pages=36781–36786 |year=2000 |doi=10.1074/jbc.M006480200 |pmid=10973974}}
5. ^{{cite journal |vauthors=Takeshita K, Bacon KB, Gantner F | title = Critical role of L-selectin and histamine H4 receptor in zymosan-induced neutrophil recruitment from the bone marrow: comparison with carrageenan | journal = J. Pharmacol. Exp. Ther. | volume = 310 | issue = 1 | pages = 272–80 | year = 2004 | pmid = 14996947 | doi = 10.1124/jpet.103.063776 }}
6. ^Bioreagents.com: Histamine H4 Receptor
7. ^Salem A, Rozov S, Al-Samadi A, et al. Histamine metabolism and transportare deranged in human keratinocytes in oral lichen planus. Br J Dermatol. 2016. Available at: https://dx.doi.org/10.1111/bjd.14995.
8. ^{{cite journal |vauthors=Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP | title = Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells | journal = J. Pharmacol. Exp. Ther. | volume = 305 | issue = 3 | pages = 1212–21 | year = 2003 | pmid = 12626656 | doi = 10.1124/jpet.102.046581 }}
9. ^{{cite journal |vauthors=Shin N, Coates E, Murgolo NJ, Morse KL, Bayne M, Strader CD, Monsma FJ | title = Molecular modeling and site-specific mutagenesis of the histamine-binding site of the histamine H4 receptor | journal = Mol. Pharmacol. | volume = 62 | issue = 1 | pages = 38–47 |date=July 2002 | pmid = 12065753 | doi = 10.1124/mol.62.1.38}}
10. ^{{cite journal |vauthors=Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M | title = Crystal structure of rhodopsin: A G protein-coupled receptor | journal = Science | volume = 289 | issue = 5480 | pages = 739–45 |date=August 2000 | pmid = 10926528 | doi = 10.1126/science.289.5480.739| citeseerx = 10.1.1.1012.2275 }}
11. ^{{cite journal |vauthors=Kiss R, Kiss B, Könczöl A, Szalai F, Jelinek I, László V, Noszál B, Falus A, Keseru GM | title = Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening | journal = J. Med. Chem. | volume = 51 | issue = 11 | pages = 3145–53 |date=June 2008 | pmid = 18459760 | doi = 10.1021/jm7014777 | laysummary = http://blog.mcule.com/2011/06/as-first-post-in-mcule-blog-we-thought.html | laysource = blog.mcule.com }}
12. ^{{cite journal |vauthors=Shimamura T, Shiroishi M, Weyand S, Tsujimoto H, Winter G, Katritch V, Abagyan R, Cherezov V, Liu W, Han GW, Kobayashi T, Stevens RC, Iwata S | title = Structure of the human histamine H(1) receptor complex with doxepin | journal = Nature | volume = 475| issue = 7354| pages = 65–70|date=June 2011 | pmid = 21697825 | doi = 10.1038/nature10236 | url = | pmc=3131495}}
13. ^{{cite journal |vauthors=Schultes S, Nijmeijer S, Engelhardt H, Kooistra AJ, Vischer HF, de Esch IJ, Haaksma EJ, Leurs R, de Graaf C | title = Mapping histamine H₄ receptor-ligand binding modes | journal = MedChemComm | volume = 4 | issue = | pages = 193–204 | year = 2013 | month = | pmid = | doi = 10.1039/C2MD20212C }}
14. ^{{cite journal |vauthors=Nijmeijer S, Engelhardt H, Schultes S, van de Stolpe AC, Lusink V, de Graaf C, Wijtmans M, Haaksma EE, de Esch IJ, Stachurski K, Vischer HF, Leurs R | title = Design and pharmacological characterization of VUF14480, a covalent partial agonist that interacts with cysteine 98(3.36) of the human histamine H₄ receptor. | journal = Br J Pharmacol | volume = 170 | issue = 1 | pages = 89–100| year = 2013 | month = | pmid = 23347159 | doi = 10.1111/bph.12113| pmc = 3764852}}
15. ^InterPro: IPR008102 Histamine H4 receptor
16. ^{{cite journal | last1 = Varga | first1 = C | last2 = Horvath | first2 = K | last3 = Berko | first3 = A | last4 = Thurmond | first4 = RL | last5 = Dunford | first5 = PJ | last6 = Whittle | first6 = BJ. | year = 2005 | title = Inhibitory effects of histamine H4 receptor antagonists on experimental colitis in the rat | url = | journal = European Journal of Pharmacology | volume = 522 | issue = 1–3| pages = 130–8 | doi = 10.1016/j.ejphar.2005.08.045 | pmid = 16213481 }}
17. ^{{cite journal | last1 = Coruzzi | first1 = G | last2 = Adami | first2 = M | last3 = Guaita | first3 = E | last4 = de Esch | first4 = IJ | last5 = Leurs | first5 = R. | year = 2007 | title = Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenan-induced acute inflammation | url = | journal = European Journal of Pharmacology | volume = 563 | issue = 1–3| pages = 240–4 | doi = 10.1016/j.ejphar.2007.02.026 | pmid = 17382315 }}